Structural Analysis of Inhibitor Binding Site of Enzyme by Neutron Crystallography

人类免疫缺陷病毒蛋白I(HIVPR)是治疗获得性免疫缺陷综合征的重要药物靶蛋白之一。为了高效的药物发现，获取HIVPR活性部位结合水分子的结构信息对于有效的抑制剂的结合是非常重要的。由于HIVPR涉及自降解，因此设计了单链和交联型HIVPR。合成了HIVPR和HIVPR，并用X-射线单晶衍射法测定了它们的三级结构。所设计的HIV-PR将用于从动力学和热力学的角度评价新设计的缓蚀剂的亲和力，并用于制备用于中子结晶学的大晶体。

Human immune deficiency virus protease–I (HIVPR) is one of the important drug target proteins for the acquired immune deficiency syndrome. For the efficient drug discovery, it is of importance to obtain structural information of bound water molecules at the active site of HIVPR for the binding of potent inhibitors. Since HIVPR involves the self-degradation, the single-chained and cross-linked HIVPR were designed. The both HIVPR were prepared, and their tertiary structure was determined by X-ray crystallography. The designed HIV-PR will be useful for evaluate the affinity of newly designed inhibitors from kinetic and thermodynamic point of view and preparation of large crystal for neutron crystallography.